Exercise training, but not resveratrol, improves metabolic and inflammatory status in skeletal muscle of aged men

Key points Ageing is associated with lifestyle‐related metabolic diseases, and exercise training has been suggested to counteract such metabolic deteriorations. The natural antioxidant resveratrol has been reported to exert ‘exercise‐like’ health beneficial metabolic and anti‐inflammatory effects in rodents, but little is known about the metabolic effects of resveratrol supplementation alone and in combination with exercise training in humans. The present findings showed that exercise training markedly improved muscle endurance, increased content and activity of oxidative proteins in skeletal muscle and reduced markers of oxidative stress and inflammation in skeletal muscle of aged men. Resveratrol alone did not elicit metabolic effects in healthy aged subjects, but even impaired the exercise training‐induced improvements in markers of oxidative stress and inflammation in skeletal muscle. Abstract The aim was to investigate the metabolic and anti‐inflammatory effects of resveratrol alone and when combined with exercise training in skeletal muscle of aged human subjects. Healthy, physically inactive men (60–72 years old) were randomized to either 8 weeks of daily intake of 250 mg resveratrol or placebo or to 8 weeks of high‐intensity exercise training with 250 mg resveratrol or placebo. Before and after the interventions, resting blood samples and muscle biopsies were obtained and a one‐legged knee‐extensor endurance exercise test was performed. Exercise training increased skeletal muscle peroxisome proliferator‐activated receptor‐γ co‐activator‐1α mRNA ∼1.5‐fold, cytochrome c protein ∼1.3‐fold, cytochrome c oxidase I protein ∼1.5‐fold, citrate synthase activity ∼1.3‐fold, 3‐hydroxyacyl‐CoA dehydrogenase activity ∼1.3‐fold, inhibitor of κB‐α and inhibitor of κB‐β protein content ∼1.3‐fold and time to exhaustion in the one‐legged knee‐extensor endurance exercise test by ∼1.2‐fold, with no significant additive or adverse effects of resveratrol on these parameters. Despite an overall ∼25% reduction in total acetylation level in skeletal muscle with resveratrol, no exclusive resveratrol‐mediated metabolic effects were observed on the investigated parameters. Notably, however, resveratrol blunted an exercise training‐induced decrease (∼20%) in protein carbonylation and decrease (∼40%) in tumour necrosis factor α mRNA content in skeletal muscle. In conclusion, resveratrol did not elicit metabolic improvements in healthy aged subjects; in fact, resveratrol even impaired the observed exercise training‐induced improvements in markers of oxidative stress and inflammation in skeletal muscle. Collectively, this highlights the metabolic efficacy of exercise training in aged subjects and does not support the contention that resveratrol is a potential exercise mimetic in healthy aged subjects.